Redundant functions of phospholipases D1 and D2 in platelet α-granule release
Redundant functions of phospholipases D1 and D2 in platelet α-granule release
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DOI：
10.1111/j.1538-7836.2012.04924.x
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发表时间：
2012-11-01
影响因子：
10.4
通讯作者：
Nieswandt, B.
中科院分区：
文献类型：
--
作者：
Thielmann, I.;Stegner, D.;Nieswandt, B.
背景：血小板活化和聚集对于原发性止血至关重要，但也可导致闭塞性血栓形成。激动剂诱导的血小板活化涉及导致磷脂酶活化的不同信号通路，磷脂酶产生第二信使。磷脂酶C（PLC）在血小板活化中的作用已得到公认，但磷脂酶D（PLD）的相关性知之甚少。目的和方法：本研究的目的是确定PLD 2在血小板生理学中的潜在功能。因此，我们通过产生缺乏PLD 2或PLD 1和PLD 2两者的小鼠来研究PLD 2在血小板信号传导和血栓形成中的功能。在体外和体内分析PLD缺陷血小板的粘附、活化和聚集。结果如下：而PLD 2的缺乏导致血小板中PLD活性降低，它在体外和体内对细胞的功能没有可检测的影响。然而，两种PLD亚型的联合缺乏导致缺陷的α-颗粒释放和保护在FeCl 3诱导的小动脉血栓形成模型中，在仅缺乏一种PLD亚型的小鼠中未观察到这种效应。结论：这些结果揭示了PLD 1和PLD 2在血小板α颗粒分泌中的冗余作用，并表明这可能与病理性血栓形成有关。
Background: Platelet activation and aggregation are crucial for primary hemostasis, but can also result in occlusive thrombus formation. Agonist-induced platelet activation involves different signaling pathways leading to the activation of phospholipases, which produce second messengers. The role of phospholipase C (PLC) in platelet activation is well established, but less is known about the relevance of phospholipase D (PLD) . Objective and methods: The aim of this study was to determine a potential function of PLD2 in platelet physiology. Thus, we investigated the function of PLD2 in platelet signaling and thrombus formation, by generating mice lacking PLD2 or both PLD1 and PLD2. Adhesion, activation and aggregation of PLD-deficient platelets were analyzed in vitro and in vivo. Results: Whereas the absence of PLD2 resulted in reduced PLD activity in platelets, it had no detectable effect on the function of the cells in vitro and in vivo. However, the combined deficiency of both PLD isoforms resulted in defective alpha-granule release and protection in a model of FeCl3-induced arteriolar thrombosis, effects that were not observed in mice lacking only one PLD isoform. Conclusion: These results reveal redundant roles of PLD1 and PLD2 in platelet alpha-granule secretion, and indicate that this may be relevant for pathologic thrombus formation.